Immune mechanisms operating in mosquitoes are capable of limiting or preventing the development of filarial worms within these vectors. Although melanotic encapsulation reactions are responsible for resistance in certain species of mosquitoes, parasites are often capable of developing in other closely related species or even other strains, of the same species. Why certain mosquito species respond effectively while others do not, or why a species can immunologically destroy one parasite species but not another, are questions of fundamental relevance to our understanding of vector-parasite compatibility. The objective of the proposed research is to elucidate immune recognition and effector mechanisms and their regulation in mosquitoes exposed to filarial worms. Various biochemical and molecular techniques will be used with the mosquitoes Aedes aegypti, Aedes trivittatus and the filarial worms Brugia malayi, B. pahangi and Dirofilaria immitis (1) quantitatively assess the role specific enzymes and substrates might play in the production of protein-polyphenol complexes required for the immune destruction of microfilariae in mosquitoes, (2) identify and characterize hemolymph proteins that are uniquely or preferentially expressed in mosquitoes during melanotic encapsulation reactions, (3) characterize functional differences in mosquito hemocytes using lectins and anti-hemocyte monoclonal antibodies, and (4) begin characterizing immune mechanisms operating in the Armigeres subalbatus-Brugia spp. vector-parasite system that allows the development of B. pahangi but results in the immune destruction of B. malayi. The proposed studies will provide an increased clarification of mechanisms of immune responses in mosquitoes and a greater insight into vector-parasite associations, thereby increasing our understanding of the epidemiology of mosquito-borne filariasis.